Monoclonal antibodies, representing the three major serum isotypes, derived both from hybridoma cultures and serum antibodies with phosphocholine binding activities were studied for their protective effect in mice challenged with various capsular types of live pneumococci. Using the standardized intraperitoneal challenge assay with the pneumococci, used to characterize antisera for passive immunization of humans with pneumococcal disease, it was found that antibodies with phosphocholine specificity provided protection against lethal challenge with some but not all pneumococcal types. These experiments, using standardized assays, confirmed the reports of Briles et al. that antibodies with phosphocholine specificity had protective affect against lethal challenge with encapsulated pneumococci. We found some exceptions to this observation; 1) antibodies of the IgA type do not confer protection confirming the need for complement-mediated activities initiated by antibodies. 2) Not all antibodies with phosphocholine binding activity conferred immunity. 3) Antiserum, induced by a pneumococcus encapsulated with the C polysaccharide conferred a high degree of specific activity against challenge with several pneumococcal types. Rabbit antiserum, with phosphocholine specificity elicited by injection of type 27 pneumococci, yielded no protection. The ability of antibodies with phosphocholine specificity to precipitate with the non-capsular cell extracts of various pneumococci was found to correlate with the ability to protect against lethal infection with these various types. The evidence indicated that the phosphocholine containing structure eliciting the protective antibodies was the cell was polysaccharide. The cell wall polysaccharide can be detected on all encapsulated pneumococci.